Genetic Mapping of Non-Insulin Dependent Diabetes The genetics of non-insulin dependent diabetes mellitus (NIDDM; Type 2 diabetes; adult onset diabetes) will be investigated using linkage analysis with DNA probes revealing restriction fragment length polymorphisms (RFLPs). NIDDM affects 5% of the adult population of the U.S. and complications of the disease make it one of the leading causes of death in this country. NIDDM is familial in mature, and thus is an appropriate subject for genetic investigation. The long term goals are to develop a DNA probe test for the presymptomatic diagnosis of NIDDM and to isolate and characterize the gene(s) which cause NIDDM. We will search for linkage in one large family segregating maturity onset diabetes of the young (MODY) and in the Pima indian tribe which has very high incidence of NIDDM/ RFLP proves to be tested will come from the extensive, well characterized collection at Collaborative Research. By using RFLP probes which are known to be equally spaced along the chromosomes, we can systematically search for linkage. With both 2-point linkage analysis and multilocus linkage analysis we have a high probability of detecting linkage (LOD greater than or equal to 3.0) in each group (MODY family and/or Pima indians) in the first year of screening. The linked probes will be used to test for heterogeneity by analyzing NIDDM families and affected sib-pairs from the general population. With the discovery of linkage, a high resolution genetic map of the NIDDM locus (loci) will we constructed. This will require the isolation of many additional RFLP probes by the use of several directed cloning methods and will narrow the region containing the NIDDM gene to a few million base pairs. Information about the physical structure of the locus will be obtained by hybridizing the linked probes to Southern blots generated by pulse field gel electrophoresis. Under optimum conditions, experiments directed at cloning NIDDM candidate genes will be performed.